Cytogenetics in Fanconi Anemia: The Importance of Follow-Up and the Search for New Biomarkers of Genomic Instability

Fanconi Anemia (FA) is a disease characterized by genomic instability, increased sensitivity to DNA cross-linking agents, and the presence of clonal chromosomal abnormalities. This genomic instability can compromise the bone marrow (BM) and confer a high cancer risk to the patients, particularly in the development of Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). The diagnosis of FA patients is complex and cannot be based only on clinical features at presentation. The gold standard diagnostic assay for these patients is cytogenetic analysis, revealing chromosomal breaks induced by DNA cross-linking agents. Clonal chromosome abnormalities, such as the ones involving chromosomes 1q, 3q, and 7, are also common features in FA patients and are associated with progressive BM failure and/or a pre-leukemia condition. In this review, we discuss the cytogenetic methods and their application in diagnosis, stratification of the patients into distinct prognostic groups, and the clinical follow-up of FA patients. These methods have been invaluable for the understanding of FA pathogenesis and identifying novel disease biomarkers. Additional evidence is required to determine the association of these biomarkers with prognosis and cancer risk, and their potential as druggable targets for FA therapy.     

Exceeding hemoglobin target levels in US hemodialysis patients receiving epoetin, 1999 to 2002

Despite emerging concerns that exceeding anemia targets with erythropoiesis stimulating agents may be risky for hemodialysis patients, the magnitude of and risk factors for the problem have received little attention, particularly regarding year-to-year comparisons. We studied monthly hemoglobin and epoetin levels in 41,101 patients aged at least 65 years who initiated hemodialysis between 1999 and 2002, with upper targets defined by hemoglobin levels of 120 and 130 g/L, respectively. While baseline hemoglobin values and epoetin doses rose from year to year, their rates of change during follow-up declined (p<0.0001). Similar patterns were seen after reaching hemoglobin levels of 110 g/L; comparing 1999 to 2002, the proportions reaching 120 and 130 g/L in the ensuing 9 months increased from 90% to 96% (p<0.0001) and from 56% to 69%, respectively (p<0.0001). Multivariate analysis showed that, while more recent years of dialysis inception and initial epoetin dose were associated with all 3 outcomes, higher baseline hemoglobin levels were associated with reaching levels of 110 and 120 g/L, but not 130 g/L. Exceeding hemoglobin level targets has become widespread in the United States and is associated with changes in epoetin dosing practices.     

Dialysis patients treated with Epoetin alfa show improved anemia symptoms: A new analysis of the Canadian Erythropoietin Study Group trial

The health‐related quality of life (HRQOL) claims in the current Epoetin alfa label are based on the reanalyses of the exercise and physical function data from the Canadian Erythropoietin Study Group trial. The reanalysis was done to comply with the Food and Drug Administration's requirement of using statistical methods that are currently standard in evaluating clinical trial data. Presented here are HRQOL results associated with anemia. The Canadian Erythropoietin Study Group trial was a multicenter, double blind, randomized, placebo‐controlled trial evaluating the effects of Epoetin alfa on HRQOL in anemic hemodialysis patients. A total of 118 patients who were 18–75 years old, on hemodialysis for >3 months, who had a hemoglobin <9.0 g/dL, and did not have coronary artery disease or diabetes mellitus, were randomized to either receive placebo (n=40), or receive intravenous Epoetin alfa to achieve a target hemoglobin of 9.5–11.0 g/dL (n=40) or a target of 11.5–13.0 g/dL (n=38). Patients were followed for 6 months. The two Epoetin alfa‐treatment groups were combined for all analyses performed. This post hoc analysis was conducted using an intent‐to‐treat repeated measures mixed model analysis of variance using Bonferroni's multiplicity correction. The Epoetin alfa‐treated group showed a statistically significant improvement in the Kidney Disease Questionnaire symptom of fatigue in comparison with placebo. Additionally, the change in hemoglobin at 2 months was correlated with change in fatigue, energy, shortness of breath, and weakness, but had minimal effect on depression. These analyses confirm previously reported results, which indicate that treating hemodialysis patients with an erythropoiesis‐stimulating agent improves HRQOL.     

Environmental exposure of lead and iron deficit anemia in children age ranged 1-5 years: A cross sectional study

Iron (Fe) deficiency is the most common nutritional problem among children and lead (Pb) toxicity is the most common environmental health threat to children all over the world. The objective of this study was to determine blood lead (BPb) levels and prevalence of Fe deficient anemia among 1 to 5 year old children attending day care clinic in pediatric ward of civil hospital Karachi, Pakistan. A total of 340 children of both genders participating in this study, were screened for anemia. Among them 215 were anemic and 125 non-anemic. The anemic group was further divided in two groups on the basis of % hemoglobin (Hb), mild (Hb < 10 g/dL) and severe anemic group (Hb < 8 g/dL), while non-anemic as referent children (Hb > 10 g/dL). The blood samples were analysed for Pb and Fe, along with hematological parameters. The result indicated that anemic children had a higher mean values of Pb in blood than referent children with Hb > 10 g/dL. The Pb levels < 100 μg/L were detected in 40% referent children while 60% of them had > 10 μg/dL. The BPb concentration in severe anemic children (53%) was found in the range of 100-200 μg/L, whereas 47% had > 200 μg/L. The significant negative correlations of BPb level with % Hb (r = −0.514 and r = −0.685) and Fe contents (r = −0.522, r = −0.762, p < 0.001) were observed in mild and severe anemic children respectively. While positive correlation was observed between BPb and age of both group and genders (r = 0.69, p < 0.01). The BPb levels were significantly associated with biochemical indices in the blood which have the potential to be used as biomarkers of Pb intoxication and Fe deficient anemia.     

Digital imaging,spectroscopy, and liquid crystals in a hand‐held,non‐invasive device to determine hemoglobin concentration

Abstract— Anemia is a significant public‐health concern both in the United States and throughout the world. This disorder of low hemoglobin concentration in the blood, which often lurks undetected for long periods, contributes significantly to mortality and morbidity and is a major cause of lost revenues from workforce shortfalls, particularly in developing countries where the incidence of anemia is higher due to malnutrition and parasitic disease. The gold standard for measuring hemoglobin is a blood test requiring phlebotomy and laboratory quantification. Current physical examination techniques and non‐invasive adjuncts for detecting anemia are not sensitive and are subject to user variability. There is an urgent need for a hand‐held device which can measure hemoglobin concentration accurately, inexpensively, and non‐invasively. The evolution of a device from its early inception, which analyzed color decomposition in a digital image of the eyelid, to its final version that is a light, inexpensive, hand‐held, non‐invasive device utilizing liquid crystals to delineate the spectroscopic characteristics of the reflected light from the palpebral conjunctiva (the inside of the lower eyelid which contains many small blood vessels) and determine hemoglobin concentration in the circulating blood will be discussed. The future refinements required for bringing such a device to the market will also be discussed.     

大肠癌并发贫血的相关因素探讨

目的分析大肠癌患者的分期、血清白蛋白水平、化疗、性别、年龄等因素与贫血的相关性。方法用Access数据库界面录入2003年1月至2009年5月间收治的251例大肠癌患者病历资料,按UICC大肠癌TNM分期法(1997年)进行分期。运用SPSS12.0统计软件包分析大肠癌贫血的相关因素。结果总贫血发生率为29.88%,男性与女性贫血发生率差异无统计学意义(P>0.05);低蛋白血症和接受化疗的患者贫血发生率均明显高于血清蛋白正常与未化疗者(P<0.005);大肠癌患者不同病理分期其贫血发生率也不完全相同(P<0.05);最终进入Logistic回归模型的危险因素有3个,分别是血清白蛋白水平(X1)、化疗(X2)及分期(X3)。结论大肠癌患者贫血的发生与分期、化疗、血清白蛋白水平有一定关系。     

卤虫卵质量检验方法

卤虫卵已经普遍应用于水产养殖业,其质量至关重要。文中结合工作经验,介绍了一套卤虫卵质量指标和检测方法。卤虫卵的质量包括孵化百分率、孵化效率、孵化速率、孵化量、孵化时间、水分及杂质。     

A community food system analysis as formative research for a comprehensive anemia control program in Northern Afghanistan

Dietary strategies to reduce chronic iron deficiency anemia are still lacking for the rural poor in most developing countries. This study of 60 households (30 irrigated zone, 30 rainfed zone) in northern Afghanistan emphasized women’s seasonal food consumption and the relationships between household capacities and consumption. In both zones, iron-rich foods and foods affecting iron bioavailability were consumed in summer and winter diets. Households in the irrigated zone had more capacity for cultivation, food preservation and social networking in addition to owning more total livestock and food animals. Rainfed zone households scored higher on food preservation knowledge. Iron-rich food consumption was strongly associated with social networking and food preservation capacities, but weakly with socioeconomic proxies. Social networking showed no relationships to socioeconomic proxies. Agroecozone, social customs and food combinations should be considered in the design of health and food security programs to reduce anemia risk.

C.E.R.A. once every 4 weeks in patients with chronic kidney disease not on dialysis: The ARCTOS extension study

C.E.R.A., a continuous erythropoietin receptor activator is approved for the treatment of anemia in patients with chronic kidney disease (CKD). The ARCTOS (administration of C.E.R.A. in CKD patients to treat anemia with a twice‐monthly schedule) phase 3 study demonstrated the efficacy and safety of C.E.R.A. in correcting anemia when administered once every 2 weeks (Q2W) subcutaneously in patients with CKD not on dialysis. We assessed the feasibility and long‐term safety of converting patients who responded to treatment with C.E.R.A. Q2W to C.E.R.A. once every 4 weeks (Q4W) during a 24‐week extension period. After the core ARCTOS study period (28 weeks), 296 patients entered the 24‐week extension period. At week 29, patients who responded to C.E.R.A. Q2W during the core period were rerandomized to receive subcutaneous C.E.R.A. Q2W or Q4W. Patients in the comparator arm could receive darbepoetin alfa once weekly or Q2W. Dosage was adjusted to maintain hemoglobin (Hb) between 11 and 13 g/dL. Mean Hb levels remained stable in all groups, and were comparable at the end of the extension period (mean [standard deviation], C.E.R.A. Q2W, 11.92 [0.90] g/dL; C.E.R.A. Q4W, 11.70 [0.86] g/dL; darbepoetin alfa, 11.89 [0.98] g/dL). Mean within‐patient standard deviation values for Hb were also comparable in all groups (0.66, 0.62, and 0.65 g/dL for C.E.R.A. Q2W, C.E.R.A. Q4W and darbepoetin alfa, respectively). All treatments were well tolerated. Subcutaneous C.E.R.A. Q4W is safe and effective in maintaining stable Hb levels in patients with CKD not on dialysis following correction with subcutaneous C.E.R.A. Q2W.